The long-term objective of this proposal is to develop short, mild, general, and versatile synthetic routes to polyfunctionalized indole alkaloids. The key step in this methodology is a recently developed, palladium catalyzed, N-heteroannulation reaction of 2-nitrostyrenes employing carbon monoxide as the reducing agent. An in depth study of a variety of functionalized 2-nitrostyrenes will be undertaken to demonstrate the synthetic versatility and generality of the cyclization. General routes to compounds having an indole nucleus such as 2-fluoro-, 3-fluoro-, and 2,3-difluoroindoles, indole-2-acetic acids, indole-3- acetic acids, indole-3-acetonitriles, tryptamines, beta-carbolines, 1,2,3,4-tetrahydro-beta-carbolines, pyrrolo[4,3,2-de]quinolines, and pyrrolo[3,2d]indoles will be pursued. As a venue to demonstrate the N- heteroannulation reaction's versatility, syntheses of a number of biologically active indoles of pharmacological interest will be pursued. For example, total syntheses (or formal total syntheses) of methoxycamalexin (phytoalexin and fungitoxin), nosiheptide (antibiotic), LY-311727 (s-PLA2 inhibitor), BE 10988 (topoisomerase II inhibitor), 7- bromo-eudistomin D (antiviral), bufotenine (hallucinogens), spider venoms (neurotoxins), damirone C and CC-1065 (cytotoxins) are proposed.